This project focuses on structural design, chemical synthesis and modification of molecules important to reproductive and developmental biology, with particular emphasis on polypeptide hormones. A. A new diethylene triamine penta-acetyl1-ovine corticotropin releasing factor (DTPA-oCRF) was synthesized, purified and radiolabeled by coordination with In111. The In111-DTPA-oCRF exhibited antibody binding properties similar to the native hormone. However, the large DTPA group was found to perturb the peptide molecule for receptor bvinding activity. B. A pentadecapeptide segment of a 68,000 dalton protein coded by cytoplasmic RNA differentially expressed in gastrula embryos of Xenopus laevis was synthesized, purified and conjugated to bovine thyroglobulin. The conjugate is being used to immunize rabbits for the production of antibodies. C. A peptide corresponding to residues 15-41 of oCRF was synthesized and shown to exhibit full agonist activity but three orders less potency than the native hormone. Ten anticipated peptides elongated from residue 17 of human CRF are being synthesized and purified, and will be studied to identify the structural requirements for agonist or antagonist activity. D. The dimeric [D-Ala6]GnRH cross-linked at the carboxyl terminus by methylene chains of various length [-(CH2)n-, n=4, 6, 8, 12, 14] was two orders less active than the monomeric peptide in both receptor binding and LH releasing activities. The low activity of these dimeric hormones is attributed to the distortion of Beta-turn structure of peptide sequence which is essential for full activity. The anticipated less constrained dimers cross-linked at Eplison-amino group of [D-Lys6, Pro9-NEt]GnRH with malonic acid (Mal) and (Gly)n-Mal-(Gly)n, n=2 and 4, were synthesized and purified. These dimeric GnRH derivatives will be used to study the effect of cross-linking or microaggregation of receptors on hormonal responses.